Although Wolbachia infections are found in most Arthropods and are of clinical importance in many parasitic diseases, very little is known about the cellular mechanisms responsible for their transmission. I have previously shown that Wolbachia preferentially populates the region of fly ovary containing the somatic stem cells, both in new inoculations and in established infected lines. Tropism for the somatic stem cell niche provides a previously undetected route to reach the germ line of new hosts. That the stem cell niche continues to be a site of accumulation suggests the possibility that horizontal and vertical transmission of Wolbachia may share common mechanisms. Here I propose to investigate the molecular and cellular mechanisms underlying host-pathogen interaction using this system. The goal of the proposal is to elucidate the bacterial and host factors involved in tropism for the stem cell niche. Towards this goal I will use molecular, genetic and cell biological tools available for Drosophila research. The questions that I intend to address are: 1. Manipulation of host cell processes: Effects of niche infection in stem cell activity 2. Interplay between bacteria and the host signaling system: Genetic disruption of signaling pathways controlling stem cell function 3. Evolutionary conservation of niche targeting: Identification of stem cell niche tropism in different host- parasite associations. 4. Determination of stem cell niche tropism: Investigation of host and bacterial factors. Layman summary: Wolbachia bacteria infect insects and other invertebrates. They are associated with river blindness and other human diseases. The bacteria are maternally transmitted in the egg from one generation to the next. I have shown that Wolbachia injected into uninfected host target the stem cell niche region of the ovary, from where it can directly infect the germ line. The same route may be important for continued maintenance of the bacteria in long-term infections. Further investigation of such transmission routes should yield information on evolution and ecology of this bacterial parasite, as well as cell biological strategies for pest and disease control.